DE156354T1 - CONTROLLED OXYDATION OF MICROBIALLY PRODUCED CYSTENE-CONTAINING PROTEINS. - Google Patents

CONTROLLED OXYDATION OF MICROBIALLY PRODUCED CYSTENE-CONTAINING PROTEINS.

Info

Publication number
DE156354T1
DE156354T1 DE198585103559T DE85103559T DE156354T1 DE 156354 T1 DE156354 T1 DE 156354T1 DE 198585103559 T DE198585103559 T DE 198585103559T DE 85103559 T DE85103559 T DE 85103559T DE 156354 T1 DE156354 T1 DE 156354T1
Authority
DE
Germany
Prior art keywords
protein
synthetic
useful
biological activity
cystine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
DE198585103559T
Other languages
German (de)
Inventor
Ze'ev Berkeley California 94207 Shaked
Sidney Norman Richmond California 94805 Wolfe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis Vaccines and Diagnostics Inc
Original Assignee
Cetus Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27081941&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DE156354(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Cetus Corp filed Critical Cetus Corp
Publication of DE156354T1 publication Critical patent/DE156354T1/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/55—IL-2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/565—IFN-beta
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/811—Interferon
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/808—Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/82—Proteins from microorganisms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/82—Proteins from microorganisms
    • Y10S530/825—Bacteria
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S930/00—Peptide or protein sequence
    • Y10S930/01—Peptide or protein sequence
    • Y10S930/14—Lymphokine; related peptides
    • Y10S930/141—Interleukin
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S930/00—Peptide or protein sequence
    • Y10S930/01—Peptide or protein sequence
    • Y10S930/14—Lymphokine; related peptides
    • Y10S930/142—Interferon

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)

Abstract

57 Method of oxidizing reduced cysteine-containing microbially produced synthetic proteins, such as synthetic INF-β or synthetic IL-2, in a controlled manner so that the synthetic proteins have the same disulfide bridging as their native counterparts. The oxidation employs o-iodosobenzoate as oxidizing agent and is carried out in an aqueous medium at a pH at least about one-half pH unit less than the pK, of the cystines to be oxidized, a synthetic protein concentration of less than about 5 mg ml. and an oxidizing agent:protein mol ratio that is at least stoichiometric, provided that the oxidizing agent is in excess in the terminal portion of the reaction.

Claims (10)

EP 85 10 3559.2 Cetus Corporation Deutsche Übersetzung der Patentansprüche nach Art. 67 (1) EPÜEP 85 10 3559.2 Cetus Corporation German translation of the patent claims according to Art. 67 (1) EPC 1. Verfahren zur gesteuerten Oxidation eines vollständig reduzierten mikrobiologisch hergestellten synthetischen Proteins mit einer Aminosäuresequenz die im wesentlichen mit der eines nützlichen Proteins identisch ist, dessen Sequenz Cysteinreste enthält, die in dem nützlichen Protein intramolekular zu einem Cystinrest verbunden sind, wobei die Cysteinreste unter geringst möglicher Über-Oxidation und Bildung nicht der Konformation entsprechender Cystinreste oder Oligomere selektiv zu Cystinresten oxidiert werden, dadurch gekennzeichnet, daß man das vollständig reduzierte mikrobiologisch hergestellte synthetische Protein mit o-Iodosobenzoesäureester in einer wässrigen Phase umsetzt, in der der pH-Wert mindestens eine halbe pH-Einheit unter dem pK -Wert der genannten1. Process for the controlled oxidation of a completely reduced microbiologically produced synthetic protein with an amino acid sequence that is essentially is identical to that of a useful protein whose sequence contains cysteine residues found in the useful protein are intramolecularly connected to a cystine residue, the cysteine residues with the least possible over-oxidation and formation of nonconforming cystine residues or oligomers selectively into cystine residues are oxidized, characterized in that the completely reduced microbiologically produced synthetic protein reacts with o-iodosobenzoic acid ester in an aqueous phase in which the pH value is at least half a pH unit below the pK value of the above Cysteine liegt und in der die Konzentration des synthetischen Proteins im Reaktionsgemisch weniger als etwa 5 mg/ml beträgt und das Molverhältnis von o-Iodosobenzoesäure zu Protein mindestens stöchiometrisch ist, unter der Voraussetzung, daß der o-Iodosobenzoesäureester im letzten Abschnitt der Umsetzung im Überschuß enthalten ist.Cysteine lies and in which the concentration of the synthetic protein in the reaction mixture is less than is about 5 mg / ml and the molar ratio of o-iodosobenzoic acid is at least stoichiometric to protein, with the proviso that the o-iodosobenzoic acid ester is contained in the last section of the implementation in excess. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß2. The method according to claim 1, characterized in that das nützliche Protein ein natürliches Protein mit einer nützlichen biologischen Aktivität ist und die intramolekulare Verbindung wesentlich für die biologischethe useful protein is a natural protein with useful biological activity, and the intramolecular Connection essential to the biological Aktivität ist oder die biologische Aktivität erhöht. 35Activity is or the biological activity is increased. 35 3. Verfahren nach einem der Ansprüche 1 oder 2, dadurch gekennzeichnet, daß das Protein ß-IFN oder IL-2 ist.3. The method according to any one of claims 1 or 2, characterized in that the protein is ß-IFN or IL-2. 4. Verfahren nach einem der Ansprüche 1 - 3, dadurch ge-4. The method according to any one of claims 1 - 3, characterized in that kennzeichnet, daß der pH-Wert zwischen 5,5 und 9 liegt.indicates that the pH is between 5.5 and 9. 5. Verfahren nach einem der Ansprüche 1-4, dadurch gekennzeichnet, daß die Konzentration des synthetischen Proteins im Bereich zwischen etwa 0,3 bis etwa 0,7 mg/ml liegt.5. The method according to any one of claims 1-4, characterized in that that the concentration of the synthetic protein ranges between about 0.3 to about 0.7 mg / ml lies. 6. Verfahren nach einem der Ansprüche 1-5, dadurch gekennzeichnet, daß nach der Oxidation das oxidierte Produkt mit einem GeIfiltrations-Verfahren gereinigt wird.6. The method according to any one of claims 1-5, characterized in that that after the oxidation, the oxidized product is purified with a gel filtration process. 7. Ein oxidiertes Präparat eines synthetischen Proteins mit einer Aminosäuresequenz, die im wesentlichen mit der eines nützlichen Proteins identisch ist, dessen Sequenz Cysteinreste enthält, die in dem nützlichen Protein intramolekular zu einem Cystinrest verbunden sind, dadurch gekennzeichnet, daß es7. An oxidized preparation of a synthetic protein having an amino acid sequence essentially identical to is identical to that of a useful protein whose sequence contains cysteine residues found in the useful protein are intramolecularly linked to a cystine residue, characterized in that it (I) dieselbe Disulfidbrücke wie das natürliche nützliche Protein aufweist;(I) same disulfide bridge as the naturally useful one Having protein; (II) im wesentlichen frei von Oligomeren ist; und(II) is essentially free of oligomers; and (III) weniger als etwa 15 Gewichtsprozent Isomere ententhält, die vom natürlichen nützlichen Protein unterschiedliche Disulfidbrücken aufweisen.(III) contains less than about 15 weight percent isomers derived from the naturally beneficial protein have different disulfide bridges. 8. Präparat nach Anspruch 7, dadurch gekennzeichnet, daß es weniger als etwa 1 Gewichtsprozent Oligomere enthält.8. A preparation according to claim 7, characterized in that it contains less than about 1 percent by weight of oligomers. 9. Präparat nach einem der Ansprüche 7 oder 8, dadurch gekennzeichnet, daß das synthetische Protein ein synthetisches Mutein eines biologisch aktiven Proteins ist, das mindestens einen zur Bildung einer Disulfidbindung9. Preparation according to one of claims 7 or 8, characterized in that that the synthetic protein is a synthetic mutein of a biologically active protein, the at least one to form a disulfide bond 1 freien Cysteinrest enthält, der für die biologische Aktivität unwesentlich ist, wobei im Mutein mindestens einer der Cysteinreste deletiert ist oder durch eine andere Aminosäure ersetzt ist.1 free cysteine residue, which is insignificant for biological activity, with at least one of the cysteine residues is deleted or replaced by a different amino acid. 10. Präparat nach einem der Ansprüche 7-9, dadurch gekennzeichnet, daß das synthetische Protein ß-IFN oder IL-2 ist.10. Preparation according to one of claims 7-9, characterized in that that the synthetic protein is ß-IFN or IL-2.
DE198585103559T 1984-03-28 1985-03-26 CONTROLLED OXYDATION OF MICROBIALLY PRODUCED CYSTENE-CONTAINING PROTEINS. Pending DE156354T1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US59435184A 1984-03-28 1984-03-28
US06/661,902 US4530787A (en) 1984-03-28 1984-10-17 Controlled oxidation of microbially produced cysteine-containing proteins

Publications (1)

Publication Number Publication Date
DE156354T1 true DE156354T1 (en) 1986-03-20

Family

ID=27081941

Family Applications (3)

Application Number Title Priority Date Filing Date
DE3587873T Expired - Lifetime DE3587873T2 (en) 1984-03-28 1985-03-26 Controlled oxidation of microbially produced proteins containing cysteine.
DE198585103559T Pending DE156354T1 (en) 1984-03-28 1985-03-26 CONTROLLED OXYDATION OF MICROBIALLY PRODUCED CYSTENE-CONTAINING PROTEINS.
DE3588226T Expired - Lifetime DE3588226D1 (en) 1984-03-28 1985-03-26 Controlled oxidation of microbially produced, cysteine-containing proteins

Family Applications Before (1)

Application Number Title Priority Date Filing Date
DE3587873T Expired - Lifetime DE3587873T2 (en) 1984-03-28 1985-03-26 Controlled oxidation of microbially produced proteins containing cysteine.

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE3588226T Expired - Lifetime DE3588226D1 (en) 1984-03-28 1985-03-26 Controlled oxidation of microbially produced, cysteine-containing proteins

Country Status (5)

Country Link
US (1) US4530787A (en)
EP (2) EP0156354B1 (en)
AT (2) ATE108186T1 (en)
CA (1) CA1233172A (en)
DE (3) DE3587873T2 (en)

Families Citing this family (82)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4925919A (en) * 1984-04-25 1990-05-15 Roland Mertelsmann Purified interleukin 2
US4992271A (en) * 1982-09-23 1991-02-12 Cetus Corporation Formulation for lipophilic IL-2 proteins
US4853332A (en) * 1982-10-19 1989-08-01 Cetus Corporation Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of biologically active proteins
JPS60115528A (en) * 1983-11-28 1985-06-22 Takeda Chem Ind Ltd Human interleukin-2 protein, its production and pharmacological composition containing the same
US4604377A (en) * 1984-03-28 1986-08-05 Cetus Corporation Pharmaceutical compositions of microbially produced interleukin-2
US4569790A (en) * 1984-03-28 1986-02-11 Cetus Corporation Process for recovering microbially produced interleukin-2 and purified recombinant interleukin-2 compositions
EP0158487B1 (en) * 1984-04-09 1991-08-28 Takeda Chemical Industries, Ltd. Stable composition of interleukin-2
US4908434A (en) * 1984-04-25 1990-03-13 Sloan-Kettering Institute For Cancer Research Process for preparing purified interleukin-2
US4908433A (en) * 1984-04-25 1990-03-13 Sloan-Kettering Institute For Cancer Research Uses of interleukin-2
US4761375A (en) * 1984-05-08 1988-08-02 Genetics Institute, Inc. Human interleukin-2 cDNA sequence
US4572798A (en) * 1984-12-06 1986-02-25 Cetus Corporation Method for promoting disulfide bond formation in recombinant proteins
CA1340265C (en) 1985-01-18 1998-12-15 Kirston E. Koths Oxidation resistant muteins
US5248769A (en) * 1985-06-26 1993-09-28 Cetus Oncology Corporation Process for recovering refractile bodies containing heterologous proteins from microbial hosts
US4748234A (en) * 1985-06-26 1988-05-31 Cetus Corporation Process for recovering refractile bodies containing heterologous proteins from microbial hosts
US4690915A (en) * 1985-08-08 1987-09-01 The United States Of America As Represented By The Department Of Health And Human Services Adoptive immunotherapy as a treatment modality in humans
DE3537708A1 (en) * 1985-10-23 1987-04-23 Boehringer Mannheim Gmbh METHOD FOR ACTIVATING T-PA AFTER EXPRESSION IN PROKARYONTS
US4766205A (en) * 1985-11-13 1988-08-23 Beatrice Companies, Inc. Method for isolation of recombinant polypeptides in biologically active forms
US4933433A (en) * 1986-01-31 1990-06-12 E. I. Du Pont De Nemours And Company Recombinant interleukin-2 composition and process for making it
CA1291706C (en) * 1986-04-03 1991-11-05 Alfred Rudolph COMBINATION THERAPY USING INTERFERON-.beta. AND INTERLEUKIN-2
DE3611817A1 (en) * 1986-04-08 1987-10-15 Boehringer Mannheim Gmbh METHOD FOR RENATURING PROTEINS
US5425940A (en) * 1986-04-09 1995-06-20 Cetus Oncology Corporation Combination therapy using interleukin-2 and tumor necrosis factor
US4777242A (en) * 1986-10-10 1988-10-11 Phillips Petroleum Company Purification of recombinant tumor necrosis factor
US5013653A (en) 1987-03-20 1991-05-07 Creative Biomolecules, Inc. Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage
CA1339757C (en) * 1987-04-16 1998-03-17 Robert F. Halenbeck Production of purified biologically active, bacterially produced recombinant human csf-1
US4929700A (en) * 1987-04-16 1990-05-29 Cetus Corporation Production of purified, biologically active, bacterially produced recombinant human CSF-1
WO1988008428A1 (en) * 1987-04-28 1988-11-03 Amgen Inc. Method for purifying granulocyte/macrophage colony stimulating factor
US4961969A (en) * 1987-05-11 1990-10-09 Cetus Corporation Process for recovering microbially produced interferon-β
US4931543A (en) * 1987-05-11 1990-06-05 Cetus Corporation Process for recovering microbially produced interleukin-2
DE3855986T2 (en) * 1987-05-11 1998-02-05 Chiron Corp PROCESS FOR OBTAINING CLEANED, OXIDIZED, RENATURED, RECOMBINANT INTERLEUKIN-2 FROM MICROORGANISMS
US4801691A (en) * 1987-05-15 1989-01-31 International Minerals & Chemical Corp. Method for removing sodium dodecyl sulfate from sodium dodecyl sulfate solubilized protein solutions
US4985544A (en) * 1987-08-04 1991-01-15 Kyowa Hakko Kogyo Co., Ltd. Process for renaturing fish growth hormone
US5004605A (en) * 1987-12-10 1991-04-02 Cetus Corporation Low pH pharmaceutical compositions of recombinant β-interferon
US5759815A (en) * 1988-02-11 1998-06-02 Creative Biomolecules, Inc. Production of platelet derived growth factor (PDGF) an muteins thereof
CA1340586C (en) * 1988-09-23 1999-06-08 Cetus Corporation Process for recovering microbially produced interferon-beta
JP2682061B2 (en) * 1988-10-07 1997-11-26 藤沢薬品工業株式会社 Method for forming intramolecular disulfide bond of peptide
US5204256A (en) * 1989-09-06 1993-04-20 Behringwerke Aktiengesellschaft Process for the purification of plasminogen activator inhibitor 2 (pai-2)
US5023323A (en) * 1990-09-12 1991-06-11 Monsanto Company Method of somatotropin naturation
US5830452A (en) * 1990-11-20 1998-11-03 Chiron Corporation Method for enhancing the anti-tumor therapeutic index of interleukin-2
WO1992009623A1 (en) * 1990-11-23 1992-06-11 Roussel-Uclaf METHOD FOR PREPARING A PROTEIN COMPRISING AT LEAST ONE INTRAMOLECULAR DISULPHIDE BOND BY OXIDATION, AT A pH OF LESS THAN 5.0, OF THE REDUCED RECOMBINANT PROTEIN
DE4105480A1 (en) * 1991-02-21 1992-08-27 Boehringer Mannheim Gmbh IMPROVED ACTIVATION OF RECOMBINANT PROTEINS
US20030171292A1 (en) * 1992-06-01 2003-09-11 Creasey Abla A. Method for using lipoprotein associated coagulation inhibitor to treat sepsis
US6063764A (en) * 1992-06-01 2000-05-16 Washington University & Chiron Corp. Method for using lipoprotein associated coagulation inhibitor to treat sepsis
AU687763B2 (en) * 1992-10-20 1998-03-05 Central Laboratory Of The Netherlands Red Cross Blood Transfusion Service Interleukin-6 receptor antagonists
US5545723A (en) * 1994-03-15 1996-08-13 Biogen Inc. Muteins of IFN-β
EP1935431A3 (en) 2000-05-15 2008-08-13 Health Research, Inc. Cancer treatments by using a combination of an antibody against her2 and interleukin-2
IL157713A0 (en) 2001-03-29 2004-03-28 Schering Corp Aryl oxime-piperazines useful as ccr5 antagonists
US6887462B2 (en) 2001-04-09 2005-05-03 Chiron Corporation HSA-free formulations of interferon-beta
PL374506A1 (en) * 2001-10-15 2005-10-31 Chiron Corporation Treatment of severe pneumonia by administration of tissue factor pathway inhibitor (tfpi)
RU2344128C2 (en) 2003-03-24 2009-01-20 Ф.Хоффманн-Ля Рош Аг Benzylpyridazinones as inhibitors of reverse transcriptase
CN100408090C (en) 2003-07-11 2008-08-06 舍林股份公司 Recombinant human interferon-beta-1b polypeptides
ES2346977T3 (en) 2003-11-04 2010-10-22 Novartis Vaccines And Diagnostics, Inc. THERAPY PROCEDURE FOR CANCERES THAT EXPRESS THE ANTIGEN CD40.
CA2560103A1 (en) * 2004-03-17 2005-11-24 Chiron Corporation Treatment of severe community-acquired pneumonia by administration of tissue factor pathway inhibitor (tfpi)
ES2318916B1 (en) * 2005-02-07 2010-03-22 Chiron Corporation PROCEDURE TO PREPARE ALDESLEUKINA FOR PHARMACEUTICAL USE.
WO2007045573A1 (en) 2005-10-19 2007-04-26 F. Hoffmann-La Roche Ag Phenyl-acetamide nnrt inhibitors
ATE503744T1 (en) 2006-08-16 2011-04-15 Hoffmann La Roche NON-NUCLEOSIDIC REVERSE TRANSCRIPTASE INHIBITORS
KR101475091B1 (en) 2006-12-13 2014-12-22 에프. 호프만-라 로슈 아게 2-(piperidin-4-yl)-4-phenoxy- or phenylamino-pyrimidine derivatives as non-nucleoside reverse transcriptase inhibitors
CA2687747C (en) 2007-05-30 2015-11-17 F. Hoffmann-La Roche Ag Non-nucleoside reverse transcriptase inhibitors
EP2207890A4 (en) * 2007-10-05 2010-12-15 Barofold Inc High pressure treatment of aggregated interferons
CA2709348C (en) 2007-12-21 2016-07-19 F. Hoffmann-La Roche Ag Non-nucleoside reverse transcriptase inhibitors for treating human immunodeficiency virus (hiv-1) mediated diseases
WO2011113601A1 (en) 2010-03-17 2011-09-22 Biogenerix Ag Method for obtaining biologically active recombinant human g-csf
CA2860170C (en) 2010-12-22 2022-06-14 The Board Of Trustees Of The Leland Stanford Junior University Superagonists and antagonists of interleukin-2
EP2683395B1 (en) 2011-03-11 2018-08-01 Assistance Publique - Hôpitaux de Paris Use of low dose il-2 for treating type 1 diabetes
CN103930433A (en) * 2011-10-21 2014-07-16 泰福生技股份有限公司 Separation of acetylated proteins from unacetylated proteins
US10183061B2 (en) 2013-06-25 2019-01-22 Icm (Institut Du Cerveau Et De La Moelle Epiniere) Boosting Treg cells for treating Alzheimer disease and related disorders
WO2015042707A1 (en) 2013-09-24 2015-04-02 Medicenna Therapeutics Pte Ltd Interleukin-2 fusion proteins and uses thereof
EP2918285A1 (en) 2014-03-11 2015-09-16 Université Pierre et Marie Curie (Paris 6) Interleukin-2 for treating food allergy
WO2015164815A1 (en) 2014-04-24 2015-10-29 The Board Of Trustees Of The Leland Stanford Junior University Superagonists, partial agonists and antagonists of interleukin-2
US10457716B2 (en) 2014-08-06 2019-10-29 University Of Notre Dame Du Lac Protein folding and methods of using same
WO2016057651A1 (en) 2014-10-09 2016-04-14 Dana-Farber Cancer Institute, Inc. Multiple-variable il-2 dose regimen for treating immune disorders
CN108135841B (en) 2015-10-22 2024-03-05 艾尔图制药公司 Pharmaceutical compositions of IL-2
US10961310B2 (en) 2017-03-15 2021-03-30 Pandion Operations, Inc. Targeted immunotolerance
WO2018217989A1 (en) 2017-05-24 2018-11-29 Pandion Therapeutics, Inc. Targeted immunotolerance
JP7433051B2 (en) 2017-06-19 2024-02-19 メディシナ セラピューティクス インコーポレイテッド Uses and methods of IL-2 superagonists, agonists, and fusions thereof
US10946068B2 (en) 2017-12-06 2021-03-16 Pandion Operations, Inc. IL-2 muteins and uses thereof
US10174091B1 (en) 2017-12-06 2019-01-08 Pandion Therapeutics, Inc. IL-2 muteins
EP3752178A1 (en) 2018-02-16 2020-12-23 Iltoo Pharma Use of interleukin 2 for treating sjögren's syndrome
WO2020007937A1 (en) 2018-07-03 2020-01-09 Iltoo Pharma Use of interleukin-2 for treating systemic sclerosis
EP3836954A1 (en) 2018-08-13 2021-06-23 Iltoo Pharma Combination of interleukin-2 with an interleukin 1 inhibitor, conjugates and therapeutic uses thereof
JP2022533702A (en) 2019-05-20 2022-07-25 パンディオン・オペレーションズ・インコーポレイテッド MAdCAM-targeted immune tolerance
EP4090674A4 (en) 2020-01-14 2024-01-24 Synthekine Inc Biased il2 muteins methods and compositions
EP4107187A1 (en) 2020-02-21 2022-12-28 Pandion Operations, Inc. Tissue targeted immunotolerance with a cd39 effector
EP4114440A1 (en) 2020-03-06 2023-01-11 Centre Hospitalier Universitaire de Nimes Low dose human interleukin-2 for the treatment of amyotrophic lateral sclerosis

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4061538A (en) * 1973-04-04 1977-12-06 Sandoz Ltd. Enzymatically oxidizing interferon
ZA803943B (en) * 1979-07-31 1981-06-24 Hoffmann La Roche Homogeneous fibroblast interferon and method for manufacture thereof
US4414147A (en) * 1981-04-17 1983-11-08 Massachusetts Institute Of Technology Methods of decreasing the hydrophobicity of fibroblast and other interferons
US4411993A (en) * 1981-04-29 1983-10-25 Steven Gillis Hybridoma antibody which inhibits interleukin 2 activity
US4405601A (en) * 1981-05-21 1983-09-20 Cancer Research Center Extraction and purification of biologically active lymphokines
US4478744A (en) * 1982-01-25 1984-10-23 Sherwood Medical Company Method of obtaining antibodies
US4450103A (en) * 1982-03-01 1984-05-22 Cetus Corporation Process for recovering human IFN-β from a transformed microorganism
EP0091539B2 (en) * 1982-03-31 1996-11-27 Ajinomoto Co., Inc. Gene coding for interleukin-2 polypeptide, recombinant DNA carrying said gene, cell lines possessing the recombinant DNA,and method for producing interleukin-2 using said cells
EP0092163B1 (en) * 1982-04-20 1988-09-28 Sloan-Kettering Institute For Cancer Research Purification of interleukin 2
JPS58201794A (en) * 1982-05-17 1983-11-24 Toray Ind Inc Purification of human interferon through concentration
US4462940A (en) * 1982-09-23 1984-07-31 Cetus Corporation Process for the recovery of human β-interferon-like polypeptides
FI82266C (en) * 1982-10-19 1991-02-11 Cetus Corp Process for Preparation of IL-2 Mutein
US4432895A (en) * 1982-11-24 1984-02-21 Hoffmann-La Roche Inc. Monomeric interferons
GR79124B (en) * 1982-12-22 1984-10-02 Genentech Inc
ATE107356T1 (en) * 1983-03-25 1994-07-15 Celltech Ltd METHOD OF PRODUCING A PROTEIN.
GB8317880D0 (en) * 1983-07-01 1983-08-03 Searle & Co Structure and synthesis of interferons
US4569790A (en) * 1984-03-28 1986-02-11 Cetus Corporation Process for recovering microbially produced interleukin-2 and purified recombinant interleukin-2 compositions

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EP0156354A2 (en) 1985-10-02
DE3587873D1 (en) 1994-08-11
EP0606673B1 (en) 2000-10-04
EP0606673A2 (en) 1994-07-20
EP0156354A3 (en) 1987-10-28
ATE108186T1 (en) 1994-07-15
EP0156354B1 (en) 1994-07-06
CA1233172A (en) 1988-02-23
DE3587873T2 (en) 1994-10-20
US4530787A (en) 1985-07-23
ATE196769T1 (en) 2000-10-15
US4530787B1 (en) 1993-07-20
DE3588226D1 (en) 2000-11-09
EP0606673A3 (en) 1995-01-25

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